Leptin Directly Depolarizes Preproglucagon Neurons in the Nucleus Tractus Solitarius

• DOI: 10.2337/db10-0128
• Publication Date: 2010-06-04T02:24:48Z
• Authors: Kazunari Hisadome; Frank Reimann; Fiona M. Gribble; Stefan Trapp
• Keywords: Solitary tract; Solitary nucleus

OBJECTIVE Glucagon-like peptide (GLP)-1 inhibits food intake, acting both in the periphery and within central nervous system. It is unclear if gut-derived GLP-1 can enter brain, or whether from preproglucagon (PPG) cells lower brainstem required to activate receptors. Brainstem PPG neurons, however, have been poorly characterized, due difficulties identifying these while viable. This study provides data on electrical properties of their regulation by orexigenic anorexigenic peptides. RESEARCH DESIGN AND METHODS Transgenic mice expressing Venus under control promoter were used identify neurons vitro slice preparations for electrophysiological recordings. RESULTS The majority spontaneously active. Further molecular characterization revealed that receptor activation had no pre- postsynaptic effect lack Similarly, they unresponsive PYY ghrelin. In contrast, leptin rapidly reversibly depolarized neurons. Responses stimulation solitary tract suggest are mostly second-order receiving direct input vagal afferent fibers. Both evoked spontaneous excitatory currents predominantly glutamatergic. CONCLUSIONS introduces PPG-promoter-Venus transgenic as a viable important tool cells. neuron activity directly modulated but was unaffected other satiety hunger Direct synaptic suggests peripheral signals (including GLP-1) could modulate via afferents.